My research focuses on understanding mechanism of transformation from precursor disease (monoclonal gammopathy of undetermined significance, MGUS; and smoldering myeloma, SMM) to multiple myeloma, and on identifying deregulated signaling proteins that can be targeted with novel therapeutic agents.
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more Prior studies have shown cytogenetic abnormalities contribute to multiple myeloma pathogenesis and disease progression. We are currently conducting molecular profiling analysis designed to discover mutations in MGUS/SMM, and in paired samples from patients who progressed to multiple myeloma. We hypothesize that patients with MGUS/SMM accumulate distinct somatic oncogenic mutations and/or acquire epigenetic changes that play a role in the progression from precursor state to multiple myeloma. As part of our ongoing therapeutic program we have tested (pre-clinically and clinical trials), e.g., MEK inhibitors and second/third generation proteasome inhibitors. Also, we are developing immune cell anti-tumor strategies using, e.g., anti-KIR monoclonal antibody and second generation immunomodulatory drugs to facilitate NK and T-cell derived tumor killing. Based on preclinical studies, we develop/conduct investigator-initiated clinical (phase I and II) studies built on extensive correlative science. Our clinical program include natural history studies focusing on molecular profiling of MGUS and SMM patients; early treatment studies for high-risk SMM patients; and rationale treatment studies for newly diagnosed and for relapse/refractory multiple myeloma patients. Furthermore, to better detect early high-risk precursor disease and to define the role of imaging strategies to monitor treatment responses, we have developed a program focusing on functional imaging (e.g., whole body-PET/MRI, novel PET/CT tracers) in MGUS/SMM and multiple myeloma patients.
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